1. Field of the Invention
The present invention is concerned with novel peptide compounds having long-lasting enkephalin agonist activity, with pharmaceutical compositions containing said novel peptide compounds as active ingredients, with use of said novel peptide compounds in methods of treating pain and schizophrenia, and with a novel method of preparing the novel peptide compounds of the present invention wherein X is sulfur.
2. Brief Description of the Prior Art
Enkephalin is an endogenous, morphine-like pentapeptide discovered by Hughes and Kosterlitz in 1975 (Hughes, J. et al., Nature, 258, 577-579, 1975) which may have either of the following two structures:
______________________________________ Methionine enkephalin: Tyr--Gly--Gly--Phe--Met Leucine Enkephalin: Tyr--Gly--Gly--Phe--Leu ______________________________________
Since the discovery of enkephalin, a great deal of activity has been devoted to investigating the mode of action of enkephalin, as well as the properties of various synthetic analogs of enkephalin. See, for example, Restak, Sat. Rev., 3-5-77, pp. 7-11; Synder, C&EN, Nov. 28, 1977, pp. 26-35; Pert et al., Nature, 269, 73-75, 1977; Klee, "Endogenous Opiate Peptides", Peptides in Neurobiology, Plenum Press, N.Y., pp. 375-396, 1977; C&EN, Aug. 16, 1976, pp. 18-19; and British Patent No. 2,008,121.
With regard to the novel method of preparing the novel peptide compounds of the present invention wherein X is sulfur, while Kametani et al., in Heterocycles, Vol. 9, No. 7, pp. 831-840 (1978), disclose an acid-catalyzed cyclization reaction of secondary amides possessing a mercapto group at the with aldehydes to give tetrahydro-1,3-thiazin-4-ones, there is no teaching or suggestion therein that the method disclosed therein would be useful in preparing compounds of the type represented by the novel peptide compounds of the present invention wherein X is sulfur.